Transcript Neurologic Complications of HIV Infection

Neurologic Complications
of HIV Infection
History
• In 1985 –virus isolated from CSF, brain, spinal
cord, peripheral nerves of patients with AIDS.
• virus, pleocytosis, and elevated
immunoglobulins in the CSF of 2/3 after
seroconversion
• central nervous system was infected both
early and asymptomatically
General Mechanisms
– direct neurotoxicity due to the neurotrophic
nature of the virus
– autoimmune disease due to immune
dysregulation
– opportunistic infections
– cerebrovascular complications, neoplasms, side
effects of retroviral therapy
– malnutrition and vitamin deficiencies
• HAART tx lead to almost 50% decrease in
incidence of HIV dementia
• Infected macrophages carry HIV into the nervous
system
• HIV-related neurologic disease becomes obvious
after the development of AIDS (CD4 <200)
• 90% of infected individuals manifesting some
form of neurologic involvement by the time of
death
Brain
Primary HIV and autoimmune
• HIV-associated dementia or encephalopathy (children)
• Demyelinating syndromes
• Parkinsonism and other movement disorders
• Sleep disorders
Neurologic opportunistic processes
• Toxoplasmosis encephalitis, progressive multifocal
leukoencephalopathy
• Cytomegalovirus and varicella zoster virus encephalitis
• Fungal: aspergillus, mucormycosis, histoplasmosis
• Bacterial: tuberculosis, syphilis
• Neoplasm: primary central nervous system lymphoma
Medications
• Neuroleptic sensitivity
Meninges
Primary HIV and autoimmune
• Acute aseptic or chronic meningitis
Neurologic opportunistic processes
• Cryptococcal meningitis
• Bacterial: tuberculosis, syphilis
• Neoplasm: lymphomatous meningitis
Spinal cord
Primary HIV and autoimmune
• Vacuolar myelopathy
Neurologic opportunistic processes
• Herpesviruses: varicella zoster virus,
cytomegalovirus, Herpes simplex virus
• Bacterial: syphilis, tuberculosis
• Neoplasm: metastatic lymphoma
Root and plexus
Neurologic opportunistic processes
• Cytomegalovirus polyradiculitis, syphilis,
tuberculosis
• Neoplasm: lymphomatous meningitis
Nerve
Primary HIV and autoimmune
• Distal symmetrical polyneuropathy
• Diffuse infiltrative lymphomatosis syndrome
• Acute and chronic inflammatory demyelinating polyneuropathies
• Mononeuritis multiplex
• Motor neuron disease
Neurologic opportunistic processes
• Cytomegalovirus mononeuritis multiplex
• Varicella zoster virus (multidermatomal)
Medications
• Nucleosides: didanosine, zalcitabine, stavudine, Dapsone,
metronidazole, isoniazid, pyridoxine, vincristine
Muscle
Primary HIV and autoimmune
• Inflammatory myopathy
Neurologic opportunistic processes
• Toxoplasmosis
Medications
• Zidovudine, trimethoprim-sulfamethoxazole
• Statins
• New-onset neurologic complications often are
superimposed on an ongoing process with a
different etiology
• The first consideration must be the stage of
systemic HIV infection, which influences both
the risk of neurologic disease as well as
possible etiologies
• Risk depends CD4 count, past and current
exposure to infectious agents, HAART agents,
use of antibacterial prophylaxis
• CD4 count provides critical information to
guide evaluation
CD4 Cell Count: >500/mm3
Infectious complications
• Acute retroviral syndrome
Noninfectious complications
• Acute inflammatory demyelinating
polyneuropathy
• Mononeuritis multiplex
• Aseptic meningitis
• HIV-associated headache
CD4 Cell Count: <200/mm3
Infectious complications
• Cytomegalovirus encephalitis and polyradiculitis
• Progressive multifocal
• Leukoencephalopathy (PML)
• Toxoplasmosis encephalitis
• Cryptococcosis meningitis
Noninfectious complications
• HIV-associated dementia
• HIV-associated polymyositis
• Vacuolar myelopathy
• Distal sensory polyneuropathy
• Diffuse infiltrative lymphomatosis syndrome
CD4 Cell Count: 200 to 500/mm3
Infectious complications
• Herpes zoster (multidermatomal)
• Tuberculous meningitis
• Neurosyphilis
Noninfectious complications
• Mononeuritis multiplex
• AZT-induced myopathy
• HIV-associated headache
• Motor neuron disease
HIV Dementia
• Prevalence of 5% to 20% among untreated
AIDS patients and an annual incidence of 7%
per year
• Is an AIDS-defining illness
• Subcortical dementia - clinical triad
progressive motor (tremor, gait instability, and
loss of fine motor control), cognitive (mental
slowing, forgetfulness, and impaired
concentration) and behavioral (mania, apathy,
emotional lability) abnormalities
HIV Dementia
• Must be discriminated from other causes of
cognitive impairment.
• Must always consider opportunistic infections
• Primary CNS lymphoma can also present in
later stages of AIDS
• Multi-infarct or vascular dementia may be
considered in particular cases
• Vasculitis secondary to infection or illicit drug
use may rarely be found.
HIV Dementia
• Illicit drugs, alcohol, or prescription drugs may
account for cognitive difficulties
• Depression should also be excluded/treated
• Always r/o encephalopathy (delirium)
• Causes of dementia in the general population
may need to be considered, which will likely
become a larger issue as the HIV-infected
population ages
HIV Dementia
• Cerebral and basal ganglia atrophy and diffuse
WM hyperintensities on T2
• MRS - diminished NAA = neuronal injury
• Neuropsych testing with HIV dementia scale
• MRS identifies higher Cho/Cr in the basal ganglia,
with reduced NAA/Cr and higher MI/Cr in frontal
white matter, confirming a subcortical
predominance
• Continuous arterial spin labeled MRI shows
decrease in both caudate blood flow and volume
HIV Dementia
• Leads to a significant increase in the overall
morbidity due to AIDS.
• Increased number of hospitalizations, increased
duration of hospital stays, and decreased life
expectancy as compared to patients with
• Average life span may be as low as 6 mo unless
HAART is administered.
• With HAART impairment can be reversed to some
extent and the likelihood of survival greatly
improved
HIV Dementia
• CSF typically demonstrates a mild pleocytosis +/- protein elevation
• HIV-1 antigen, intrathecal production of anti–HIV-1 antibodies,
presence of oligoclonal bands and presence of cytokines
• CSF viral RNA levels correlate with severity of cognitive impairment
• EEG - diffuse slowing of background rhythms but lacks specificity in
the diagnosis of HIV-associated dementia or minor cognitive and
motor disorder.
• CSF interleukin-18 levels may be useful in the detection of HIVpositive patients with opportunistic infections, being elevated in
this patient population but not elevated in HIV-positive or HIVassociated dementia patients.
• Serum interleukin-18 levels are elevated in HIV-positive or HIVassociated dementia patients but not in HIV patients with
opportunistic infections or HIV-negative controls